A Phase 1b Study to Assess the Combination of Selinexor and Daratumumab in Patients with Relapsed / Refractory Multiple Myeloma Previously Exposed to Proteasome Inhibitors (PI) and Immunomodulatory Drugs (IMiDs)

Introduction - Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor, as a single agent, or in combination with PIs or IMiDs, has shown anti-MM activity in patients (pts) with relapsed or refractory multiple myeloma (RRMM). Daratumumab, an anti-CD38 monoclonal antibody, is approved for the treatment of RRMM. In this study, we aim to explore the safety and efficacy of selinexor in combination with daratumumab and low dose dexamethasone (SDd) in pts with RRMM.\

Methods - This is a phase 1b/2 dose escalation study using a standard 3+3 design. The primary endpoint is to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) for SDd. Pts were eligible if they had RRMM and had received ≥ 3 prior therapies, including a PI and IMiD. Selinexor was independently dosed escalated in 2 concurrent cohorts: once-weekly (QW, at 100 mg) or twice-weekly (BIW, at 60 mg) regimens. Daratumumab (16 mg/kg IV) was administered QW and dexamethasone (dex) was given orally 40 mg QW or 20 mg BIW.

Results - As of 15-Jul-2017, 6 pts (4 males / 2 females) have been enrolled. Three pts each have been enrolled into the 100 mg QW and 60 mg BIW cohorts. Pts have a median age of 66 years and a median of 3 (range, 3 - 7) prior treatment regimens. Adverse events include: nausea, thrombocytopenia, and anemia. Three pts in the 100 mg QW cohort tolerated the regimen well with no DLT. The 3 pts in the 60 mg BIW cohort have not yet completed DLT evaluation. Based on preliminary tolerability and efficacy, an additional 3 pts will be enrolled in the 100 mg QW cohort to establish the RP2D dose. All 3 pts from the 100 mg QW cohort had a partial response (2 unconfirmed) after C1 and remain on study.

Conclusions - Selinexor 100 mg QW, can be combined safely with daratumumab and dex. The activity observed in the first 3 pts is promising with all 3 pts responding to therapy. Enrollment is ongoing and updated data from 100 mg QW cohort, 100 mg QW expansion, and full phase 1 will be updated and presented.